scholarly journals Treatment of relapsed B-cell non-Hodgkin's lymphoma with a combination of chimeric anti-CD20 monoclonal antibodies (rituximab) and G-CSF: final report on safety and efficacy

Leukemia ◽  
2003 ◽  
Vol 17 (8) ◽  
pp. 1658-1664 ◽  
Author(s):  
L E van der Kolk ◽  
A J Grillo-López ◽  
J W Baars ◽  
M H J van Oers
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Final Report ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

Phase II Study of Rituximab in Combination With CHOP Chemotherapy in Patients With Previously Untreated, Aggressive Non-Hodgkin’s Lymphoma

2001 ◽  
Vol 19 (2) ◽  
pp. 389-397 ◽  
Author(s):  
J. M. Vose ◽  
B. K. Link ◽  
M. L. Grossbard ◽  
M. Czuczman ◽  
A. Grillo-Lopez ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Chop Chemotherapy ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle. RESULTS: The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score ≥ 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score ≥ 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission. CONCLUSION: This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score ≥ 2 warrants further investigation with a randomized study.

Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment

2000 ◽  
Vol 18 (17) ◽  
pp. 3135-3143 ◽  
Author(s):  
Thomas A. Davis ◽  
Antonio J. Grillo-López ◽  
Christine A. White ◽  
Peter McLaughlin ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Phase Iii Trial ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

PURPOSE: This phase II trial investigated the safety and efficacy of re-treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low-grade or follicular non-Hodgkin’s lymphoma who relapsed after a response to rituximab therapy. PATIENTS AND METHODS: Fifty-eight patients were enrolled onto this study, and two were re-treated within the study. Patients received an intravenous infusion of 375 mg/m2 of rituximab weekly for 4 weeks. All patients had at least two prior therapies and had received at least one prior course of rituximab, with a median interval of 14.5 months between rituximab courses. RESULTS: Most adverse experiences (AEs) were transient grade 1 or 2 events occurring during the treatment period. Clinically significant myelosuppression was not observed; hematologic toxicity was generally mild and reversible. No patient developed human antichimeric antibodies after treatment. The type, frequency, and severity of AEs in this study were not apparently different from those reported in the phase III trial of rituximab. The overall response rate in 57 assessable patients was 40% (11% complete response and 30% partial responses). Median time to progression (TTP) in responders and median duration of response (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months), respectively. These estimated medians are longer than the medians achieved in the patients’ prior course of rituximab (TTP and DR of 12.4 and 9.8 months, respectively, P > .1) and in a previously reported phase III trial (TTP in responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing in seven of 23 responders. CONCLUSION: In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure.

Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines

2005 ◽  
Vol 23 (26) ◽  
pp. 6421-6428 ◽  
Author(s):  
David G. Maloney
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Patient Specific ◽  
Chimeric Antibody ◽  
Target Antigen ◽  
Host Immune System ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.

Novel and Engineered Anti–B-Cell Monoclonal Antibodies for Non-Hodgkin’s Lymphoma

2008 ◽  
Vol 45 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Peter Martin ◽  
Richard R. Furman ◽  
Jia Ruan ◽  
Rebecca Elstrom ◽  
Jacqueline Barrientos ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Subcutaneous Injections of Low Doses of Humanized Anti-CD20 Veltuzumab for Treatment of Indolent B-Cell Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3757-3757 ◽  
Author(s):  
O. George Negrea ◽  
Steven L Allen ◽  
Kanti R. Rai ◽  
Rebecca Elstrom ◽  
Rashid Abassi ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Hodgkin's Lymphoma ◽  
B Cell Malignancies ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20 ◽  
Dose Levels

Abstract Abstract 3757 Poster Board III-693 Background Low IV doses of veltuzumab, a 2nd generation humanized anti-CD20 monoclonal antibody with structure-function differences from chimeric rituximab, have shown clinical activity in non-Hodgkin's lymphoma (Morschhauser et al., J Clin Oncol, 2009; 27:3346-53). By avoiding lengthy IV administration and the need for dedicated infusion suites, subcutaneous (SC) injections of low-dose veluzumab may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies, and this may be particularly useful in the setting of indolent disease. Methods A multicenter, phase I/II study was undertaken to evaluate the safety, tolerability, and preliminary efficacy of SC veltuzumab in previously untreated or relapsed CD20+ indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). All patients (pts) received 4 SC injections of veltuzumab 2 weeks apart at dose levels of 80, 160, or 320 mg. Efficacy was assessed by CT-based IWG (NHL) or hematology-based NCI/IWCLL (CLL) criteria 4 and 12 weeks later, with responding pts continuing follow-up. Other evaluations included AEs, safety laboratories, B-cell blood levels (CD19), serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Twenty-six pts (10M/16F, median age 64), including 15 NHL pts (12 follicular, 3 other indolent NHL; 5 treatment naïve) most with stage III or IV disease (12/15), and 11 CLL pts (4 treatment naïve) most with Rai stage II or III disease, have now received SC veltuzumab at 80 mg (3 NHL, 3 CLL), 160 mg (9 NHL, 3 CLL) or 320 mg (3 NHL, 5 CLL) dose levels. Pre-treatment with antihistamines or steroids was not required. SC veltuzumab was well tolerated with only mild, transient injection-site reactions and tenderness, and no other safety issues. To date, all HAHA response results have been negative. In NHL pts, SC veltuzumab demonstrated good bio-availability, with a slow release pattern over several days, and a mean Cmax of 18.7, 19.5 and 64.0 μg/mL at 80, 160, and 320 mg dose levels, respectively. Depletion of circulating B cells was observed starting after 1st injection. In the 15 NHL pts, the objective response rate (CR+CRu+PR) was 53% (8/15) with a complete response (CR) rate of 20% (3/15) and with 7/8 ORs currently continuing in remission, up to 6 months after treatment. The 11 CLL pts presented with mean white blood cell levels of 55K/μL (maximum 122K/μL) and achieved much lower serum veltuzumab levels, with mean Cmax values of 4.0, 2.5 and 21.0 μg/mL at the 80, 160, and 320 mg dose levels, respectively. There were no ORs, but 5 of 7 (71%) CLL pts with response assessments currently available showed stable disease with >70% decreases in B-cell levels for up to 12 weeks. Conclusions SC administration of veltuzumab is well tolerated, achieves slow but efficient delivery into the blood, and is pharmacologically active when given every 2 weeks for a total of 4 doses. In CLL with high levels of circulating leukemic cells, more frequent and prolonged dosing is likely required. However, in NHL, these low SC doses achieved sustained serum levels with objective response rates comparable to those seen even with higher IV doses. Disclosures: Negrea: Immunomedics: Research Funding. Off Label Use: veltuzumab for investigational treatment of NHL/CLL. Allen:Immunomedics: Research Funding. Rai:Immunomedics: Research Funding. Elstrom:Immunomedics: Research Funding. Abassi:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Teoh:Immunomedics: Employment. Horne:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

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